The article discusses the role of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the activity-dependent modulation of synaptic plasticity. It highlights the relationship between neuronal activity and neurotrophic regulation of synapse development and plasticity, emphasizing the mechanisms by which BDNF can achieve local and synapse-specific modulation. Key points include: 1. **Activity-Dependent Transcription and Local Translation of BDNF**: Neuronal activity regulates the transcription of the BDNF gene, and this regulation can be localized to specific synapses through the translocation and translation of BDNF mRNA. 2. **Activity-Dependent Secretion of BDNF**: BDNF is secreted locally at active synapses, and its secretion is influenced by neuronal activity. This secretion is restricted to active synapses due to factors such as the limited diffusion capacity of BDNF and the presence of truncated TrkB receptors. 3. **Activity-Dependent Modulation of BDNF Receptor Trafficking**: Neuronal activity increases the expression of BDNF receptors on the cell surface and enhances their internalization, leading to increased signaling at active synapses. 4. **Synapse-Specific Modulation**: These mechanisms ensure that BDNF acts preferentially on active synapses, distinguishing them from less active synapses. This selectivity is crucial for the precise regulation of synaptic plasticity. 5. **Clinical Implications**: The functional significance of activity-dependent BDNF secretion is supported by studies showing that BDNF gene polymorphisms are associated with cognitive functions, such as memory. The article concludes by emphasizing the importance of understanding how neurotrophins mediate activity-dependent synaptic plasticity in a local and synapse-specific manner, highlighting the need for further research to elucidate these mechanisms in vivo.The article discusses the role of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the activity-dependent modulation of synaptic plasticity. It highlights the relationship between neuronal activity and neurotrophic regulation of synapse development and plasticity, emphasizing the mechanisms by which BDNF can achieve local and synapse-specific modulation. Key points include: 1. **Activity-Dependent Transcription and Local Translation of BDNF**: Neuronal activity regulates the transcription of the BDNF gene, and this regulation can be localized to specific synapses through the translocation and translation of BDNF mRNA. 2. **Activity-Dependent Secretion of BDNF**: BDNF is secreted locally at active synapses, and its secretion is influenced by neuronal activity. This secretion is restricted to active synapses due to factors such as the limited diffusion capacity of BDNF and the presence of truncated TrkB receptors. 3. **Activity-Dependent Modulation of BDNF Receptor Trafficking**: Neuronal activity increases the expression of BDNF receptors on the cell surface and enhances their internalization, leading to increased signaling at active synapses. 4. **Synapse-Specific Modulation**: These mechanisms ensure that BDNF acts preferentially on active synapses, distinguishing them from less active synapses. This selectivity is crucial for the precise regulation of synaptic plasticity. 5. **Clinical Implications**: The functional significance of activity-dependent BDNF secretion is supported by studies showing that BDNF gene polymorphisms are associated with cognitive functions, such as memory. The article concludes by emphasizing the importance of understanding how neurotrophins mediate activity-dependent synaptic plasticity in a local and synapse-specific manner, highlighting the need for further research to elucidate these mechanisms in vivo.